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首页> 外文期刊>Journal of stroke and cerebrovascular diseases: The official journal of National Stroke Association >Transient Global Cerebral Ischemia Induces RNF213, a Moyamoya Disease Susceptibility Gene, in Vulnerable Neurons of the Rat Hippocampus CA1 Subregion and Ischemic Cortex
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Transient Global Cerebral Ischemia Induces RNF213, a Moyamoya Disease Susceptibility Gene, in Vulnerable Neurons of the Rat Hippocampus CA1 Subregion and Ischemic Cortex

机译：瞬时全球性脑缺血诱导RNF213，MOYAMOYA疾病易感基因，大鼠海马CA1次区域和缺血皮层的脆弱神经元

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The RING finger protein 213 (RNF213) is an important susceptibility gene for moyamoya disease (MMD) and is also implicated in other types of intracranial major artery stenosis/occlusion (ICAS); however, the role of RNF213 in the development of ICAS including MMD is unclear. The constitutive expression of the RNF213 gene is relatively weak in brain tissue, while information regarding the expression patterns of the RNF213 gene under cerebral ischemia, which is one of characteristic pathologies associated with ICAS, is currently limited. Our objective was to address this critical issue, and we investigated Rnf213 mRNA expression in rat brains after 5 minutes of transient global cerebral ischemia (tGCI) by occluding the common carotid arteries coupled with severe hypotension. Rnf213 gene expression patterns were investigated with in situ RNA hybridization and a real-time polymerase chain reaction (PCR) from 1 to 72 hours after tGCI. In situ RNA hybridization revealed a significant increase in Rnf213 mRNA levels in the hippocampus CA1 sub-region 48 hours after tGCI. The significant induction of the Rnf213 gene was also evident in the ischemic cortex. Double staining of Rnf213 mRNA with NeuN immunohistochemistry revealed Rnf213 hybridization signal expression exclusively in neurons. The real-time PCR analysis confirmed the induction of the Rnf213 gene after tGCI. The up-regulation of the Rnf213 gene in vulnerable neurons in the hippocampus CA1 after tGCI suggests its involvement in forebrain ischemia, which is an underlying pathology of MMD. Further investigations are needed to elucidate its exact role in the pathophysiology of ICAS including MMD.
机译：环形手指蛋白213（RNF213）是Moyamoya疾病（MMD）的重要易感性基因，也涉及其他类型的颅内主要动脉狭窄/闭塞（ICA）;然而，RNF213在包括MMD的ICA的发展中的作用尚不清楚。 RNF213基因的组成型表达在脑组织中相对较弱，而关于脑缺血的RNF213基因表达模式的信息目前有限。我们的目标是解决这一关键问题，通过封闭与严重的低血压结合的常见颈动脉，在短暂的全局脑缺血（TGCI）之后，我们在大鼠大脑中研究了RNF213 mRNA表达。在TGCI后1至72小时，用原位RNA杂交和实时聚合酶链反应（PCR）研究RNF213基因表达模式。原位RNA杂交揭示了在TGCI后48小时的海马CA1亚区的RNF213 mRNA水平显着增加。 RNF213基因的显着诱导在缺血皮层中也明显明显。 RNF213 mRNA与Neun免疫组织化学的双重染色揭示了神经元的RNF213杂交信号表达。实时PCR分析证实了TGCI后RNF213基因的诱导。 TGCI后海马CA1在海马CA1中的脆弱神经元中RNF213基因的上调表明其参与前脑缺血，这是MMD的潜在病理学。需要进一步调查来阐明其在ICA的病理生理学中的确切作用，包括MMD。

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